Update On Lipomatous Tumors: Old Standbys and New Concepts
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1 Update On Lipomatous Tumors: Old Standbys and New Concepts John R. Goldblum, M.D. Chairman, Department of Anatomic Pathology Cleveland Clinic Professor of Pathology Cleveland Clinic Lerner College of Medicine Cleveland, Ohio
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3 Benign Lipomatous Tumors (WHO, 2002) Lipoma Lipoblastoma Angiolipoma Myolipoma Chondroid lipoma Angiomyolipoma Myelolipoma Hibernoma Spindle cell / pleomorphic lipoma
4 Lipomatous Tumors of Intermediate Malignancy (WHO, 2002) Atypical lipomatous tumor (Well-differentiated liposarcoma)
5 Malignant Lipomatous Tumors (WHO, 2002) Dedifferentiated liposarcoma Myxoid liposarcoma Round cell liposarcoma Pleomorphic liposarcoma Mixed-type liposarcoma Liposarcoma, NOS
6 Liposarcoma Atypical lipomatous tumor (well-differentiated liposarcoma) lipoma-like sclerosing inflammatory spindle cell dedifferentiated Myxoid / round cell liposarcoma Pleomorphic liposarcoma
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9 Pseudolipoblasts Fat atrophy Hibernoma cells Silicone reaction Signet ring cells Fixation artifact Neoplastic fat infiltration
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12 Problematic Lipomas Intramuscular lipoma Lipoma with hibernomatous change Lipoma with fat necrosis Cellular angiolipoma Spindle cell / pleomorphic lipoma Chondroid lipoma
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22 CD34
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25 CD34
26 Spindle Cell / Pleomorphic Lipoma Well-circumscribed subcutaneous mass Shoulder, neck, back Striking male predominance No recurrence / metastasis CD34-positive Common cytogenetic abnormality (16q, 13q )
27 Pleomorphic Lipoma Differential Diagnosis Atypical lipomatous tumor Pleomorphic sarcoma
28 ALT/WDL: A Historical Perspective Evans (1979) Recur Dediff Mets Died Subcutis (9) Deep soft tissue (13) 69% Retroperitoneum (8) 62% %
29 Evans (1979) Subcutis Deep soft tissue Retroperitoneum Atypical lipoma Atypical intra- WDL muscular lipoma
30 ALT/WDL: A Historical Perspective Weiss & Rao (1992) Recur Dediff Mets Died Deep soft tissue 43% 6% 0% 0% (46) Retroperitoneum 91% 17% 17% 33% (23) Weiss SW et al, AJSP 1992
31 Weiss (1992) Subcutis Deep soft tissues Retroperitoneum Atypical lipoma WDL WDL
32 ALT/WDL: Lumper or Splitter? Lumpers Call all tumors (regardless of site) Call all tumors (regardless of site) Splitters Superficial (subcutis) Deep (deep soft tissue/retro) ALT WDL Atypical lipoma WDL * Requires communication and understanding between pathologist and surgeon/oncologist!
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37 When To Suspect ALT/WDL Large and deep fatty tumor (when it comes in buckets!) Retroperitoneal fatty tumor (with rare exceptions) MRI heterogeneity (surgeon is suspicious) Fibrous bands Atypia (hyperchromasia) identified at low power *Don t look for lipoblasts!!
38 Courtesy of Dr. F. Pédeutour
39 MDM2 amplification
40 MDM2 Amplification: Utility of FISH Benign lipomatous tumors (n=30) 0/30 Lipoma 0/10 Angiolipoma 0/10 SCL/PL 0/9 Lipoblastoma 0/1 ALT/WDLS (n=13) 13/13 Dediff LS (n=14) 14/14 MDM2 amplification Weaver J et al. Mod Pathol 2008
41 MDM2
42 Pleomorphic Lipoma vs ALT PL ALT/WDL Atypical cells Yes Yes Floret cells characteristic sometimes Ropey collagen Yes No CD34 Yes Rare cells MDM2 ampl No Yes Dedifferentiation No Sometimes
43 ALT / WDL Low-grade sarcoma (no metastatic capability) incomplete excision complete excision Local recurrence Cured! Tumor progression Metastasis
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46 MDM2
47 Retroperitoneal MFH : Does It Exist? 25 Retroperitoneal MFH 17 reclassified as DDLS 8 classified as undifferentiated sarcoma Extensive sampling revealed foci of ALT/WDL MDM2/CDK4 immunoreactivity 12q13-15 amplification (CGH) *most retroperitoneal MFH actually represent dedifferentiated areas of a DDLS Coindre et al, Mod Pathol 2003
48 Myxoid / Round Cell Liposarcoma Second most common subtype of liposarcoma Peak Age: 5th decade (not in children < 10 years) Extremities (thigh, popliteal fossa)
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56 Criteria for Round Cell Liposarcoma Closely packed round cells with highgrade nuclei Little/no intervening myxoid stroma Obliteration of characteristic plexiform vascular pattern
57 Transitional / Hypercellular Zones More cellular than typical myxoid liposarcoma but not fulfilling criteria for round cell liposarcoma No proven prognostic significance of transitional areas Warrant increasing to Grade II/III?
58 Myxoid/Round Cell Liposarcoma Cytogenetics t(12;16)(q13;p11) t(12;22)(q13;q12) DDIT3 (CHOP)/FUS DDIT3 (CHOP)/EWSR1
59 RODH-4 STAT6 DDIT3 OS-9 KUB3 SHGC DDIT3 (12q13) Break-Apart Probe SO SG ~134 kb ~700 kb gap ~660kb Myxoid/Round Cell Liposarcoma
60 Pleomorphic Liposarcoma Rarest subtype of liposarcoma Adults (6th-7th decade); M > F Most arise in deep soft tissues of extremities Trunk Retroperitoneum Inguinal region Head and neck
61 Pleomorphic Liposarcoma Histologic Patterns MFH-like with focal lipoblastic differentiation Sheets of bizarre lipoblasts Epithelioid variant
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65 Pleomorphic Liposarcoma Author Recurrence Metastasis Death F/U (median) Mentzel (24) 21% 29% 38% 24 mos Downes (17) 29% 47% 53% 25 mos Miettinen (10) % 6.5 mos
66 Pleomorphic Sarcomas - Cytogenetics 46 pleomorphic sarcomas (most originally diagnosed as MFH) Most displayed highly complex karyotypes No aberration specific for any subgroup Not useful in subclassifying pleomorphic sarcomas Mertens F et al. Genes Chrom Cancer, 1998
67 Well-differentiated Lipomatous Tumors Cytogenetics Lipoma Hibernoma Lipoblastoma Spindle / pl lipoma ALT / WDL 12q, 6p, 13q 11q 8q 16q, 13q ring chromosomes (12q)
68 Liposarcoma Category ALT/WDL Cytogenetics Ring/giant marker chromosomes (12q13-15) Dedifferentiated Additional complex aberrations Myxoid/round cell t(12;16)(q13;p11) Pleomorphic Complex aberrations
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